FDA Workshop on “Emerging Infectious Diseases:

Evaluation to Implementation for Transfusion

and Transplantation Safety”

Day 1: “Evaluating Emerging Infectious Diseases (EIDs) for Transfusion Safety”

May 11, 2010

Paul A. Mied, Ph.D.Update for the Blood Products Advisory Committee

July 26, 2010

Goal of the EID Workshop

To explore strategies for EID threat detection, intervention, and the prioritization of effort

Key Questions

1. How do we and should we characterize the risk to blood safety from an EID?

2. What are the criteria to prioritize EIDs that pose a threat to blood safety?

3. How should regulators, blood organizations, manufacturers, and other stakeholders develop a response to the threat from EIDs?

Emerging Infectious Diseases

New infections Re-emerging infections Drug-resistant infections

whose incidence in humans has increased within the past 20 years or whose incidence threatens to increase in the near future.

Factors that Contribute to the Emergence and Spread of Infectious Diseases

Physical Environmental Factors Genetic and Biological Factors Ecological Factors Social, Political, and Economic Factors

- human demographics, behavior, and sanitation - closer human contact with wildlife and its habitat - failure of control measures - international travel and commerce - microbial adaptation and change - human susceptibility to infection - climate and weather

Surveillance

the ongoing systematic collection, analysis, and interpretation of outcome-specific data

↓

needs to be disseminated in a timely fashion

Some Thoughts about EIDs

About 70% of our 68 or so EIDs have been zoonotic

New threats will emerge; many will be zoonotic Key will be:

- “to unite human and veterinary medicine - to anticipate potential threats to blood safety - to be vigilant for early detection

↓ Improve predictive capability, coordination

and communication through strong national and international partnerships”

Horizon Scanning

the systematic examination of potential threats, opportunities, and likely developments

the ability to detect novel and unexpected issues, persistent problems, or trends

Repositories of Specimens

Specific purpose for each TTVS, RADAR, and TRIPS linked donor-

recipient Repositories Contributions of each Repository

- evaluation of transfusion-transmission of known agents

- may be very useful for that purpose for new and future EID agents

Critical Information about an EID

Is the agent blood-borne? Is there an asymptomatic blood-borne phase? Have transfusion transmissions been observed? Does the agent survive component mfg and storage? Does the agent cause disease? What is the disease attack

rate, severity, mortality, treatability of the disease? What is the prevalence and incidence in donors? Is it

significant? Is there professional, regulatory, and public concern? Are interventions available? What would be the impact of those interventions on

resources?

AABB TTD EID 4-Year Project

Goals: 1. To describe known and potential EID

agents for which transfusion transmission is documented or its potential exists, and no effective intervention exists;

2. To create fact sheets for the agents; 3. To prioritize agents as to their blood

safety threat.

Perspectives on Prioritization

“Prioritization is not the main function. We get a feel for which ones have significant risk that requires us to take action.”

“If you can develop a multi-pathogen (detection) chip or pathogen reduction, the question of prioritization becomes moot”

“It’s more difficult to factor in public perception and the societal concerns”

“We acted because a test was available; but the paradigm has changed for test manufacturers”

“We acted in the face of a disease: SFV: No TTD XMRV: No TTD?”

Key Questions on Prioritization

“What is acceptable risk?” “When do we act with an

intervention? And, when an intervention is introduced, can it be removed if it is no longer needed?”

“How do we know when a trigger for action is reached?”

Two EID Case Studies 1. Babesia

- expanding geographically- regional testing is conceivable

2. XMRV

- no transfusion transmission observed - no known causative relationship to disease- donor prevalence is unknown- test methods have not been standardized - literature is controversial: inconsistent findings for viral markers

The Precautionary Principle

“ Action should be taken even if its value cannot be proven; that is, even if there is only a theoretical risk of harm.

If risk is possible, then we must err on the side of caution.”

How do we Prioritize Our Response to an EID Threat?

“We could develop a scoring system or a formula for prioritizing”

We could develop an “EID Agent Priority Matrix”

EID Agent Priority Matrix

Stramer et. al. 2009 Transfusion 49: Suppl.

Plasmodia

B19 virus

absent

very low

low

moderate

high

theoretical very low low moderate high

Science/Epidemiology

CW

D

Ch

iku

ngu

nya

vir

us

SL

E v

iru

s

HIV

var

iant

s

In

flu

enza

vir

us

sub

typ

e H

5N1

Pu

blic

Per

cep

tion

HH

V-8

HA

V

SFVD

engu

e vi

ruse

s

vCJD

Bab

esiaL

eish

man

ia

T. c

ruzi

B. b

urg

dorf

eri

“ XMRV is an excellent model”

Deliberate action plan Does it cause disease? Is it transfusion transmitted? A model for the future

“WNV was a very good model”

Developed a Model: Likely to be transfusion transmitted

Infection; disease; epidemiology; a test in place

“What’s the appropriate action now?”

Babesia: “Implementing blood donor testing is an option that could be considered”

XMRV: “Continue research and perhaps consider implementing an interim blood safety intervention”

Decision-making Framework of Health Canada

3 phases:

1. Issue Identification: identify a possible risk to blood safety;

2. Risk Assessment by surveillance and hemovigilance; Benefit Assessment;

3. Risk Management: identify and analyze options, select and implement strategy, monitor results; surveillance

Risk Assessment Hazard Identification Dose Response Assessment for the

infectious agent Exposure Assessment:

distributions, not point estimates Risk Characterization Risk Management: Risks vs

Benefits, compare “what-ifs”

What do we Need to Manage EID Risks?

“Stronger links with other governments, regulatory authorities and public health.”

“Increased networking of researchers; global coordination of responses to EIDs.”

“Collaboration and communication with our domestic and international stakeholders.”

“A forum to describe how the decisions that were made were made.”

Question: “What is the appropriate vehicle or process to put this forum into action?”

Tools to Address EIDs

TessArae High Multiplicity Resequencing Pathogen Microarrays (RPM)

Technologies for prion protein assays and blood filters that are under development

Pathogen Reduction Technology (PRT) - Expectations vs realities - Perceived costs vs potential benefits of lower infection

rates and eliminating some current tests. - “Combining methods may offer advantages: Orthogonal process approach was suggested – combines

NAT and PRT to cover the Window Period. Could Testing + Inactivation or Removal = Reduced Deferrals?”

Final Questions

What do we do about lack of interest and participation from the manufacturers due to the small market and margins?

Where will the funding come from as threats emerge or current technology becomes antiquated?